Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV003238800 | SCV003936793 | likely pathogenic | not provided | 2023-01-03 | criteria provided, single submitter | clinical testing | Reported with a second GLB1 variant, phase unknown, in a patient with infantile GM1-gangliosidosis (Higaki et al., 2011); Published functional studies demonstrate M480V reduced beta-galactosidase activity to approximately 10% of wild-type (Takai et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21520340, 29396849, 23337983) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689842 | SCV005185641 | likely pathogenic | Mucopolysaccharidosis, MPS-IV-B | 2024-05-17 | criteria provided, single submitter | clinical testing | Variant summary: GLB1 c.1438A>G (p.Met480Val) results in a conservative amino acid change located in the Beta-galactosidase 1-like , first all-beta domain (IPR048912) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249584 control chromosomes. c.1438A>G has been reported in the literature in at least one compound heterozygous individual affected with GM1-Gangliosidosis (e.g. Higaki_2011). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of beta-galatosidase activity in vrito (e.g. Takai_2013). The following publications have been ascertained in the context of this evaluation (PMID: 21520340, 23337983). ClinVar contains an entry for this variant (Variation ID: 553636). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV000669124 | SCV005658087 | likely pathogenic | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2024-05-22 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000669124 | SCV000793838 | uncertain significance | GM1 gangliosidosis type 2; GM1 gangliosidosis type 3; Mucopolysaccharidosis, MPS-IV-B; Infantile GM1 gangliosidosis | 2017-09-01 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |